Data Sets

Datasets were searched for using the same filters as before - must be human tissue that expressed lewy bodies, must have at least 3 patients and 3 controls, and must…

10 datasets were identified:

CodeID Tissue/Cell type Variant Samples Type of array GEO Ref Comments PIs
DIJ Substantia Nigra not specified 15 disease, 8 control Affymetrix Human Genome U133 Plus 2.0 Array GSE49036 Has some Braak staging Dijkstra AA, Ingrassia AI, de Menezes RX, van Kesteren RE, Rozemuller AM, Heutink P, vandeBerg WJ
FFR Substantia Nigra not specified 9 replicates for the controls and 16 replicates for the Parkinson’s disease patients Affymetrix Human Genome U133 Plus 2.0 Array GSE7621 Ffrench-Mullen JM
MOR.SN Substantia nigra, split into medial and lateral portions sporadic 15 samples of medial parkinsonian SN, 9 samples of lateral parkinsonian SN (24), 8 medial nigra control samples and 7 lateral nigra control samples(15) Affymetrix Human Genome U133A Array GSE8397 Age and sex Moran LB, Graeber MB
MID1 Substantia Nigra pars compacta not specified 10 PD brain samples and 8 control Affymetrix Human Genome U133 Plus 2.0 Array GSE20141 Middleton FA, Kim PD, Zhang-James Y, Davis RL
MID2 Whole substantia nigra not specified 18 controls, 11 patients Affymetrix Human Genome U133A Array GSE20292 Age and sex Middleton FA, James M, Zhang Y, Davis RL
DUM Cortex (BA9) not specified 29 PD, 44 neurologically normal controls Illumina HiSeq 2000 GSE68719 Have age of death, sex, and some samples have corresponding proteomics Dumitriu A, Golji J, Labadorf AT, Gao B, Beach TG, Myers RH, Longo KA, Latourelle JC
MOR.FC Frontal cortex sporadic 3 Controls 5 Patients Affymetrix Human Genome U133A Array GSE8397 Age and sex Moran LB, Graeber MB
LEW Dorsal Nucleus of the Vagus Nerve not specified 6 PD samples and 4 controls Affymetrix Human Genome U133A 2.0 Array GSE19587 Age and sex lewandowski nm, small sa
MID3 Prefrontal cortex not specified 15 controls 14 patients Affymetrix Human Genome U133A Array GSE20168 Age and sex Middleton FA, James M, Zhang Y, Davis RL
MID4 Putamen not specified 20 controls and 15 patients Affymetrix Human Genome U133A Array GSE20291 Age and sex Middleton FA, James M, Zhang Y, Davis RL
BOT1 Locus Coeruleus LRRK2 4 controls and 2 patients Affymetrix Human Exon 1.0 ST Array GSE34516 LC does degenerate in PD. Main source of noradrenaline. Botta-Orfila T, Sánchez-Pla A, Fernández M, Carmona F, Ezquerra M, Tolosa E
BOT2 Putamen LRRK2 5 controls and 3 patients Affymetrix Human Exon 1.0 ST Array GSE23290 NA Botta-Orfila T, Tolosa E, Gelpi E, Sànchez-Pla A, Martí M, Valldeoriola F, Fernández M, Carmona F, Ezquerra M

Quality Control - PD_QC.R

Checked data distribution using PCA and boxplots. Some of the datasets have quite mixed samples wereas others separate quite nicely into controls and patients. Boxplots didn’t suggest any samples were outliers.

Common DEGs

As before, I ran either Limma or DESeq2 and looked for common fold change direction across all 10 datasets. Filtering populations I used were ALS samples (for neurodegeneration), familial blood (for any general familial PD signal + tissue non-specific), and sporadic blood (for generic sporadic signal + tissue non-specific).

Overlap minus these filtration datasets left 210 genes this time (ALS_sfblood_ALLgenes.txt). Overlapping with Malacards PD genes shows presence of 6 PD-associated genes, including alpha synuclein itself.

> intersect(resultsup, PDgenes)
[1] "MSX1" "SPR" 
> intersect(resultsdown, PDgenes)
[1] "SNCA"    "ALDH1A1" "UCHL1"   "CYCS"  

Functional Enrichment

Functional enrichment in EnrichR for upregulated and downregulated genes.

Upregulated signal isn’t entirely clear; a number of signalling and DNA-binding pathways are enriched but not with the strongest p values. Alternatively there is quite a strong signal in the downregulated genes. A number of neurodegenerative pathways (inc Parkinson’s disease) are enriched, as well as the electron transport chain/mitochondrial processes (mitochondrion (GO:0005739) padj = 4.711e-8, 23 genes). GO Biological Process also implicates autophagy, which highlights the presence of CHMP2B - a causative ALS/FTLD gene.

VarElect of cDEGs

Symbol Description Category GIFTs Matched Phenotypes Matched Phenotypes Scount Global Rank (Total Genes 11967) Score
SNCA Synuclein Alpha Protein Coding 61 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 2 378.27
UCHL1 Ubiquitin C-Terminal Hydrolase L1 Protein Coding 62 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 7 209.64
CYCS Cytochrome C, Somatic Protein Coding 57 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 63 63.23
NDUFV2 NADH:Ubiquinone Oxidoreductase Core Subunit V2 Protein Coding 53 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 106 51.16
ALDH1A1 Aldehyde Dehydrogenase 1 Family Member A1 Protein Coding 57 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 153 42.23
SPR Sepiapterin Reductase Protein Coding 58 Parkinson’s Disease, LRRK2, late-onset 3 126 40.38
MSX1 Msh Homeobox 1 Protein Coding 55 Parkinson’s Disease, LRRK2, late-onset 3 169 33.61
NDUFS1 NADH:Ubiquinone Oxidoreductase Core Subunit S1 Protein Coding 56 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 213 28.87
NDUFS3 NADH:Ubiquinone Oxidoreductase Core Subunit S3 Protein Coding 56 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 236 26.54
SYT11 Synaptotagmin 11 Protein Coding 50 Parkinson’s Disease, LRRK2, neurodegeneration 3 239 22.93
CASP7 Caspase 7 Protein Coding 59 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 309 21.45
TOMM20 Translocase Of Outer Mitochondrial Membrane 20 Protein Coding 48 Parkinson’s Disease, LRRK2, neurodegeneration 3 362 16.56
MFN2 Mitofusin 2 Protein Coding 59 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 424 16.55
IGF1R Insulin Like Growth Factor 1 Receptor Protein Coding 66 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 435 16.27
MAP1B Microtubule Associated Protein 1B Protein Coding 51 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 474 15.18
TMEM126B Transmembrane Protein 126B Protein Coding 47 Parkinson’s Disease, LRRK2 2 363 13.45
PTS 6-Pyruvoyltetrahydropterin Synthase Protein Coding 57 Parkinson’s Disease, late-onset, neurodegeneration 3 556 11.88
CASP6 Caspase 6 Protein Coding 57 Parkinson’s Disease, LRRK2, neurodegeneration 3 573 11.74
RAB7A RAB7A, Member RAS Oncogene Family Protein Coding 58 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 759 11.00
PPP2R2B Protein Phosphatase 2 Regulatory Subunit Bbeta Protein Coding 55 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 788 10.69
PYROXD1 Pyridine Nucleotide-Disulphide Oxidoreductase Domain 1 Protein Coding 44 Parkinson’s Disease, late-onset 2 487 10.60
AGRP Agouti Related Neuropeptide Protein Coding 51 late-onset, neurodegeneration 2 504 10.27
AIFM1 Apoptosis Inducing Factor Mitochondria Associated 1 Protein Coding 59 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 898 9.70
FLT1 Fms Related Tyrosine Kinase 1 Protein Coding 62 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 952 9.26
RTN4 Reticulon 4 Protein Coding 54 LRRK2, late-onset, neurodegeneration 3 792 9.21
DYNC1H1 Dynein Cytoplasmic 1 Heavy Chain 1 Protein Coding 54 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 965 9.11
TUBA4A Tubulin Alpha 4a Protein Coding 56 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 968 9.09
CHMP2B Charged Multivesicular Body Protein 2B Protein Coding 53 Parkinson’s Disease, late-onset, neurodegeneration 3 894 8.43
RGS2 Regulator Of G Protein Signaling 2 Protein Coding 51 Parkinson’s Disease, LRRK2, neurodegeneration 3 944 8.07
HIST1H1C Histone Cluster 1 H1 Family Member C Protein Coding 48 Parkinson’s Disease 1 520 7.11
PAWR Pro-Apoptotic WT1 Regulator Protein Coding 48 Parkinson’s Disease, neurodegeneration 2 982 6.36
MS4A6A Membrane Spanning 4-Domains A6A Protein Coding 45 Parkinson’s Disease, late-onset, neurodegeneration 3 1259 6.26
MYO1C Myosin IC Protein Coding 53 Parkinson’s Disease, LRRK2, neurodegeneration 3 1362 5.78
SUMO1 Small Ubiquitin-Like Modifier 1 Protein Coding 56 Parkinson’s Disease, neurodegeneration 2 1277 5.04
ACLY ATP Citrate Lyase Protein Coding 53 Parkinson’s Disease, LRRK2, neurodegeneration 3 1577 4.91
SDHA Succinate Dehydrogenase Complex Flavoprotein Subunit A Protein Coding 56 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 1850 4.77
PGF Placental Growth Factor Protein Coding 54 LRRK2, late-onset 2 1361 4.72
TRADD TNFRSF1A Associated Via Death Domain Protein Coding 51 Parkinson’s Disease, LRRK2, neurodegeneration 3 1694 4.57
HSPA1L Heat Shock Protein Family A (Hsp70) Member 1 Like Protein Coding 52 Parkinson’s Disease, LRRK2 2 1457 4.38
GABBR2 Gamma-Aminobutyric Acid Type B Receptor Subunit 2 Protein Coding 57 Parkinson’s Disease, LRRK2, late-onset 3 1880 4.04
PGAM1 Phosphoglycerate Mutase 1 Protein Coding 54 Parkinson’s Disease, neurodegeneration 2 1602 3.95
ATP6V1E1 ATPase H+ Transporting V1 Subunit E1 Protein Coding 52 Parkinson’s Disease, LRRK2, late-onset 3 2008 3.70
FZD5 Frizzled Class Receptor 5 Protein Coding 57 Parkinson’s Disease, LRRK2 2 1718 3.67
MRPS22 Mitochondrial Ribosomal Protein S22 Protein Coding 50 Parkinson’s Disease, neurodegeneration 2 1776 3.54
PLIN2 Perilipin 2 Protein Coding 51 late-onset, neurodegeneration 2 1805 3.47
CIRBP Cold Inducible RNA Binding Protein Protein Coding 48 Parkinson’s Disease, LRRK2, neurodegeneration 3 2119 3.38
SNX10 Sorting Nexin 10 Protein Coding 49 Parkinson’s Disease, LRRK2 2 1913 3.22
FABP3 Fatty Acid Binding Protein 3 Protein Coding 54 Parkinson’s Disease, neurodegeneration 2 1947 3.13
BCAT2 Branched Chain Amino Acid Transaminase 2 Protein Coding 53 Parkinson’s Disease, neurodegeneration 2 1987 3.05
ADH1B Alcohol Dehydrogenase 1B (Class I), Beta Polypeptide Protein Coding 53 Parkinson’s Disease, late-onset 2 2004 3.03
RARRES2 Retinoic Acid Receptor Responder 2 Protein Coding 50 late-onset 1 1536 2.92
DNAJC24 DnaJ Heat Shock Protein Family (Hsp40) Member C24 Protein Coding 44 LRRK2, late-onset 2 2118 2.76
PRPF4 Pre-MRNA Processing Factor 4 Protein Coding 51 Parkinson’s Disease, LRRK2, neurodegeneration 3 2366 2.55
FLCN Folliculin Protein Coding 50 Parkinson’s Disease, late-onset 2 2227 2.46
COPS5 COP9 Signalosome Subunit 5 Protein Coding 51 Parkinson’s Disease, LRRK2, neurodegeneration 3 2450 2.31
ENOPH1 Enolase-Phosphatase 1 Protein Coding 49 Parkinson’s Disease 1 2186 1.83
ZC3HAV1 Zinc Finger CCCH-Type Containing, Antiviral 1 Protein Coding 46 Parkinson’s Disease, neurodegeneration 2 2481 1.81
PLCG1 Phospholipase C Gamma 1 Protein Coding 56 Parkinson’s Disease, LRRK2 2 2492 1.80
STAB1 Stabilin 1 Protein Coding 48 Parkinson’s Disease 1 2218 1.76
HP1BP3 Heterochromatin Protein 1 Binding Protein 3 Protein Coding 44 Parkinson’s Disease, neurodegeneration 2 2528 1.71
MLLT11 MLLT11, Transcription Factor 7 Cofactor Protein Coding 45 late-onset 1 2261 1.68
AGL Amylo-Alpha-1, 6-Glucosidase, 4-Alpha-Glucanotransferase Protein Coding 55 late-onset 1 2261 1.68
MAVS Mitochondrial Antiviral Signaling Protein Protein Coding 50 late-onset 1 2261 1.68
TAZ Tafazzin Protein Coding 52 late-onset 1 2261 1.68
SLC6A1 Solute Carrier Family 6 Member 1 Protein Coding 57 Parkinson’s Disease, neurodegeneration 2 2545 1.67
STAT4 Signal Transducer And Activator Of Transcription 4 Protein Coding 56 LRRK2, late-onset 2 2559 1.63
EIF4E Eukaryotic Translation Initiation Factor 4E Protein Coding 59 Parkinson’s Disease, LRRK2 2 2565 1.62
NIPSNAP1 Nipsnap Homolog 1 Protein Coding 49 Parkinson’s Disease, LRRK2 2 2565 1.62
RAD51C RAD51 Paralog C Protein Coding 51 Parkinson’s Disease, LRRK2 2 2573 1.60
NCALD Neurocalcin Delta Protein Coding 51 Parkinson’s Disease, LRRK2 2 2573 1.60
LRRC1 Leucine Rich Repeat Containing 1 Protein Coding 44 Parkinson’s Disease, LRRK2 2 2573 1.60
PKNOX1 PBX/Knotted 1 Homeobox 1 Protein Coding 47 Parkinson’s Disease, LRRK2 2 2573 1.60
GABARAPL1 GABA Type A Receptor Associated Protein Like 1 Protein Coding 53 Parkinson’s Disease, neurodegeneration 2 2609 1.51
MAP1LC3B Microtubule Associated Protein 1 Light Chain 3 Beta Protein Coding 52 Parkinson’s Disease, neurodegeneration 2 2611 1.50
LYVE1 Lymphatic Vessel Endothelial Hyaluronan Receptor 1 Protein Coding 51 late-onset, neurodegeneration 2 2651 1.41
DYNC1I1 Dynein Cytoplasmic 1 Intermediate Chain 1 Protein Coding 48 Parkinson’s Disease, neurodegeneration 2 2666 1.37
FOXO4 Forkhead Box O4 Protein Coding 51 Parkinson’s Disease, LRRK2 2 2667 1.37
NME3 NME/NM23 Nucleoside Diphosphate Kinase 3 Protein Coding 51 Parkinson’s Disease, neurodegeneration 2 2680 1.33
SERTAD3 SERTA Domain Containing 3 Protein Coding 38 neurodegeneration 1 2476 1.29
USP8 Ubiquitin Specific Peptidase 8 Protein Coding 57 Parkinson’s Disease, LRRK2, neurodegeneration 3 2776 1.27
ATG14 Autophagy Related 14 Protein Coding 43 Parkinson’s Disease 1 2551 1.17
LDLRAD4 Low Density Lipoprotein Receptor Class A Domain Containing 4 Protein Coding 40 Parkinson’s Disease 1 2551 1.17
TAF4 TATA-Box Binding Protein Associated Factor 4 Protein Coding 48 LRRK2, neurodegeneration 2 2778 1.03
RBL1 RB Transcriptional Corepressor Like 1 Protein Coding 51 LRRK2, late-onset 2 2802 0.95
IARS2 Isoleucyl-TRNA Synthetase 2, Mitochondrial Protein Coding 49 Parkinson’s Disease 1 2681 0.94
KLHL36 Kelch Like Family Member 36 Protein Coding 41 late-onset 1 2683 0.93
ST3GAL5 ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 5 Protein Coding 55 late-onset 1 2706 0.88
CLIC2 Chloride Intracellular Channel 2 Protein Coding 49 late-onset 1 2706 0.88
DDX42 DEAD-Box Helicase 42 Protein Coding 46 Parkinson’s Disease 1 2711 0.87
ANXA6 Annexin A6 Protein Coding 53 Parkinson’s Disease 1 2711 0.87
CCDC40 Coiled-Coil Domain Containing 40 Protein Coding 45 Parkinson’s Disease 1 2711 0.87
LAG3 Lymphocyte Activating 3 Protein Coding 44 Parkinson’s Disease 1 2711 0.87
SDCCAG3 Serologically Defined Colon Cancer Antigen 3 Protein Coding 41 Parkinson’s Disease 1 2711 0.87
BCAR3 BCAR3, NSP Family Adaptor Protein Protein Coding 49 Parkinson’s Disease 1 2711 0.87
IMP4 IMP4, U3 Small Nucleolar Ribonucleoprotein Protein Coding 42 Parkinson’s Disease 1 2711 0.87
LETMD1 LETM1 Domain Containing 1 Protein Coding 43 Parkinson’s Disease 1 2711 0.87
PTP4A1 Protein Tyrosine Phosphatase Type IVA, Member 1 Protein Coding 51 Parkinson’s Disease 1 2711 0.87
RCC1 Regulator Of Chromosome Condensation 1 Protein Coding 49 LRRK2, neurodegeneration 2 2829 0.86
TXNL1 Thioredoxin Like 1 Protein Coding 47 late-onset 1 2741 0.79
CD84 CD84 Molecule Protein Coding 51 late-onset 1 2806 0.66
DUSP9 Dual Specificity Phosphatase 9 Protein Coding 50 LRRK2 1 2807 0.66
FHIT Fragile Histidine Triad Protein Coding 54 Parkinson’s Disease, late-onset 2 2896 0.61
ANGPT2 Angiopoietin 2 Protein Coding 55 LRRK2, late-onset 2 2901 0.58
INHBB Inhibin Beta B Subunit Protein Coding 53 LRRK2, late-onset 2 2901 0.58
CALML4 Calmodulin Like 4 Protein Coding 41 LRRK2 1 2853 0.54
HDAC7 Histone Deacetylase 7 Protein Coding 52 LRRK2 1 2853 0.54
ATP2B2 ATPase Plasma Membrane Ca2+ Transporting 2 Protein Coding 54 LRRK2, neurodegeneration 2 2915 0.52
PPP2R1B Protein Phosphatase 2 Scaffold Subunit Abeta Protein Coding 57 LRRK2 1 2905 0.39
RGS4 Regulator Of G Protein Signaling 4 Protein Coding 52 LRRK2 1 2905 0.39
KPNA1 Karyopherin Subunit Alpha 1 Protein Coding 51 Parkinson’s Disease, neurodegeneration 2 2942 0.35
NRXN3 Neurexin 3 Protein Coding 51 neurodegeneration 1 2920 0.34
SARS Seryl-TRNA Synthetase Protein Coding 53 neurodegeneration 1 2920 0.34
PGRMC1 Progesterone Receptor Membrane Component 1 Protein Coding 53 neurodegeneration 1 2920 0.34
RDH16 Retinol Dehydrogenase 16 (All-Trans) Protein Coding 44 LRRK2 1 2936 0.28
SMAD6 SMAD Family Member 6 Protein Coding 54 LRRK2 1 2936 0.28
NFATC4 Nuclear Factor Of Activated T Cells 4 Protein Coding 53 LRRK2 1 2936 0.28
REEP5 Receptor Accessory Protein 5 Protein Coding 46 LRRK2 1 2936 0.28
EFNA4 Ephrin A4 Protein Coding 50 LRRK2 1 2936 0.28
MST1 Macrophage Stimulating 1 Protein Coding 55 LRRK2 1 2936 0.28
FSTL3 Follistatin Like 3 Protein Coding 48 LRRK2 1 2936 0.28
LAMA5 Laminin Subunit Alpha 5 Protein Coding 51 LRRK2 1 2936 0.28
PRC1 Protein Regulator Of Cytokinesis 1 Protein Coding 47 LRRK2 1 2936 0.28
LAMB2 Laminin Subunit Beta 2 Protein Coding 55 LRRK2 1 2936 0.28
ZNF629 Zinc Finger Protein 629 Protein Coding 38 LRRK2 1 2938 0.27
NR6A1 Nuclear Receptor Subfamily 6 Group A Member 1 Protein Coding 50 LRRK2 1 2938 0.27
ATP8A2 ATPase Phospholipid Transporting 8A2 Protein Coding 50 LRRK2 1 2938 0.27
AREL1 Apoptosis Resistant E3 Ubiquitin Protein Ligase 1 Protein Coding 38 LRRK2 1 2938 0.27
ZNF692 Zinc Finger Protein 692 Protein Coding 40 LRRK2 1 2938 0.27
ROBO3 Roundabout Guidance Receptor 3 Protein Coding 52 LRRK2 1 2938 0.27
ACAT2 Acetyl-CoA Acetyltransferase 2 Protein Coding 55 LRRK2 1 2938 0.27
STX2 Syntaxin 2 Protein Coding 48 LRRK2 1 2938 0.27
TCF3 Transcription Factor 3 Protein Coding 55 LRRK2 1 2938 0.27
RAB6B RAB6B, Member RAS Oncogene Family Protein Coding 46 LRRK2 1 2938 0.27
DOCK6 Dedicator Of Cytokinesis 6 Protein Coding 50 LRRK2 1 2938 0.27
INSIG2 Insulin Induced Gene 2 Protein Coding 47 LRRK2 1 2938 0.27
DNAJB9 DnaJ Heat Shock Protein Family (Hsp40) Member B9 Protein Coding 45 LRRK2 1 2938 0.27
HLTF Helicase Like Transcription Factor Protein Coding 48 LRRK2 1 2938 0.27
VPS4B Vacuolar Protein Sorting 4 Homolog B Protein Coding 51 Parkinson’s Disease 1 2952 0.18
SLC23A2 Solute Carrier Family 23 Member 2 Protein Coding 52 Parkinson’s Disease 1 2952 0.18
TULP2 Tubby Like Protein 2 Protein Coding 44 late-onset 1 2955 0.13
ALAS1 5’-Aminolevulinate Synthase 1 Protein Coding 53 late-onset 1 2955 0.13
PTBP2 Polypyrimidine Tract Binding Protein 2 Protein Coding 47 neurodegeneration 1 2959 0.07
ZMYND8 Zinc Finger MYND-Type Containing 8 Protein Coding 46 neurodegeneration 1 2959 0.07
WDYHV1 WDYHV Motif Containing 1 Protein Coding 39 neurodegeneration 1 2959 0.07
FAM193B Family With Sequence Similarity 193 Member B Protein Coding 42 neurodegeneration 1 2959 0.07
SEZ6L2 Seizure Related 6 Homolog Like 2 Protein Coding 46 neurodegeneration 1 2959 0.07

Protein Interaction Network

Using the 210 DEGs I seeded a network of 2429 nodes and 4097 edges.

library(biomaRt)

setwd("/Users/clairegreen/Documents/PhD/TDP-43/TDP-43_Code/Results/PPI_Network/")

PPI <- read.table("iref14_Human_UP_noDup_table_nodash.txt", header = T)
braingenes <- read.csv("Zhang_BrainCelltype_Markers_braingenes.csv", header = T)

DEG_list <- readLines("~/Documents/PhD/Parkinsons/Parkinsons_Code/Results/FamilialBlood/ALS_sfblood_ALLgenes.txt")

mart <- useMart("ENSEMBL_MART_ENSEMBL",dataset="hsapiens_gene_ensembl", host="www.ensembl.org")
attributes <- listAttributes(mart)
mart_back <- getBM(attributes =c("hgnc_symbol", "uniprotswissprot"), filters="hgnc_symbol", values=DEG_list,  mart=mart)
genelist_Uniprot <- subset(mart_back, !(mart_back$uniprotswissprot == ""))
setwd("/Users/clairegreen/Documents/PhD/Parkinsons/Parkinsons_Code/Results/FamilialBlood/")
write.csv(genelist_Uniprot, "martback.csv", row.names = F)

# IDENTIFY MISSING GENES AND FIND UNIPROT CODES FOR THEM. NB SOME GENES MAY NOT BE PROTEIN CODING #

mart_table <- read.csv("martback.csv", header = T) #A table with the uniprot codes for the DEGs
uniprot_gene <- mart_table$uniprotswissprot

DEG_PPI <- subset(PPI, PPI$V1 %in% uniprot_gene | PPI$V2 %in% uniprot_gene)
rownames(DEG_PPI) <- 1:nrow(DEG_PPI)

write.csv(DEG_PPI, "DEG_PPI_famBlood.csv", row.names = F)

## Convert Uniprot ID to HGNC symbol. Biomart jumbles output so
## Go To https://biodbnet-abcc.ncifcrf.gov/db/db2db.php submit each column of names. Select Uniprot Accession for input and Gene Symbol for output.
# Select "NO" for remove duplicate input valies

DEG_PPI <- read.csv("DEG_PPI_famBlood.csv")

DEG_PPI <- subset(DEG_PPI, DEG_PPI$Gene1 !="-")
DEG_PPI <- subset(DEG_PPI, DEG_PPI$Gene2 !="-")

write.csv(DEG_PPI, "FinalPDPPI.csv", row.names = F, quote = F)

PPI Network

Common Coexpression

I ran common coexpression again using Sharc. DUM was again removed because it had ~100,000 fewer edges than the other datasets. I then plotted the distributions of rho values to check they were normally distributed:

From this it is clear that the LEW and MOR.FC datasets do not have the power for a normal coexpression distribution. These two datasets were therefore removed from the common coexpression edge analysis.

When looking for a common edge, I tried three different minimum Rho values; 0.5, 0.4, and 0.3.

Threshold of 0.5

Threshold of 0.4

Threshold of 0.3

The largest connected component consists of 82 genes and 95 edges.

Largest Connected Component of 0.3

IrefIndex 14.0 PPI between PD Malacards and LCC

Here we can see that there are 25 LCC proteins which forming 45 PPI relationships with 25 PD Malacard genes (1 overlap of PARK7)

VarElect

Although already noted, the VarElect results clearly show the membership of PARK7 in the network. The interesting thing about PARK7 being here is that it is more commonly associated with early-onset or juvenile Parkinson’s disease. Another interesting point is that, although PARK7 PD is early-onset, it’s classified by UniProt as having “slow progression and initial good response to levodopa”.

CYCS or Cytochrome C, Somatic, is a small heme protein that functions as a central component of the electron transport chain in mitochondria. It is closely related to Parkinson’s disease in the literature due to its apparent malfuction in the disease.

Direct VarElect Results

Symbol Description Category GIFTs Matched Phenotypes Matched Phenotypes Scount Global Rank (Total Genes 11967) P-Value Score Average Disease Causing Likelihood
PARK7 Parkinsonism Associated Deglycase Protein Coding 56 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 5 270.87
CYCS Cytochrome C, Somatic Protein Coding 57 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 63 63.23
UBE2E3 Ubiquitin Conjugating Enzyme E2 E3 Protein Coding 51 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 119 48.51
STXBP1 Syntaxin Binding Protein 1 Protein Coding 57 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 370 18.76
VDR Vitamin D Receptor Protein Coding 61 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 380 18.20
COX5A Cytochrome C Oxidase Subunit 5A Protein Coding 53 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 536 13.99
PGK1 Phosphoglycerate Kinase 1 Protein Coding 59 Parkinson’s Disease, late-onset, neurodegeneration 3 513 12.40
NDUFA8 NADH:Ubiquinone Oxidoreductase Subunit A8 Protein Coding 50 Parkinson’s Disease, LRRK2, late-onset 3 641 10.77
EIF4EBP1 Eukaryotic Translation Initiation Factor 4E Binding Protein 1 Protein Coding 57 Parkinson’s Disease, LRRK2, late-onset 3 715 9.90
DLD Dihydrolipoamide Dehydrogenase Protein Coding 61 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 899 9.68
PSMC6 Proteasome 26S Subunit, ATPase 6 Protein Coding 50 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 925 9.51
PLA2G2A Phospholipase A2 Group IIA Protein Coding 56 Parkinson’s Disease, late-onset, neurodegeneration 3 770 9.43
RTN4 Reticulon 4 Protein Coding 54 LRRK2, late-onset, neurodegeneration 3 792 9.21
NDUFA5 NADH:Ubiquinone Oxidoreductase Subunit A5 Protein Coding 51 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 998 8.87
UQCRC2 Ubiquinol-Cytochrome C Reductase Core Protein 2 Protein Coding 55 Parkinson’s Disease, LRRK2, neurodegeneration 3 1033 7.46
RAB11A RAB11A, Member RAS Oncogene Family Protein Coding 55 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 1321 6.93
SFXN1 Sideroflexin 1 Protein Coding 47 Parkinson’s Disease, LRRK2, neurodegeneration 3 1241 6.34
RAB1A RAB1A, Member RAS Oncogene Family Protein Coding 51 Parkinson’s Disease, LRRK2, neurodegeneration 3 1282 6.14
PSMC5 Proteasome 26S Subunit, ATPase 5 Protein Coding 51 Parkinson’s Disease, LRRK2, neurodegeneration 3 1311 6.03
PSMA7 Proteasome Subunit Alpha 7 Protein Coding 55 Parkinson’s Disease, LRRK2, neurodegeneration 3 1482 5.27
SUMO1 Small Ubiquitin-Like Modifier 1 Protein Coding 56 Parkinson’s Disease, neurodegeneration 2 1277 5.04
ACLY ATP Citrate Lyase Protein Coding 53 Parkinson’s Disease, LRRK2, neurodegeneration 3 1577 4.91
SDHA Succinate Dehydrogenase Complex Flavoprotein Subunit A Protein Coding 56 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 1850 4.77
PSMD6 Proteasome 26S Subunit, Non-ATPase 6 Protein Coding 47 Parkinson’s Disease, LRRK2, neurodegeneration 3 1696 4.56
UQCRC1 Ubiquinol-Cytochrome C Reductase Core Protein 1 Protein Coding 50 Parkinson’s Disease, LRRK2, neurodegeneration 3 1746 4.43
PDHB Pyruvate Dehydrogenase E1 Beta Subunit Protein Coding 56 Parkinson’s Disease, LRRK2, neurodegeneration 3 1781 4.32
NR4A1 Nuclear Receptor Subfamily 4 Group A Member 1 Protein Coding 55 Parkinson’s Disease, LRRK2, neurodegeneration 3 1865 4.09
IARS Isoleucyl-TRNA Synthetase Protein Coding 55 Parkinson’s Disease, neurodegeneration 2 1597 3.97
ATP6V1E1 ATPase H+ Transporting V1 Subunit E1 Protein Coding 52 Parkinson’s Disease, LRRK2, late-onset 3 2008 3.70
MAP2K1 Mitogen-Activated Protein Kinase Kinase 1 Protein Coding 65 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 2197 3.60
PPP2CA Protein Phosphatase 2 Catalytic Subunit Alpha Protein Coding 56 Parkinson’s Disease, LRRK2, neurodegeneration 3 2050 3.58
TRIM37 Tripartite Motif Containing 37 Protein Coding 51 neurodegeneration 1 1309 3.49
UQCRFS1 Ubiquinol-Cytochrome C Reductase, Rieske Iron-Sulfur Polypeptide 1 Protein Coding 51 Parkinson’s Disease, LRRK2, neurodegeneration 3 2137 3.31
VAV1 Vav Guanine Nucleotide Exchange Factor 1 Protein Coding 57 LRRK2, late-onset 2 1938 3.15
RUNX2 Runt Related Transcription Factor 2 Protein Coding 57 late-onset 1 1481 3.04
CUL3 Cullin 3 Protein Coding 55 Parkinson’s Disease, LRRK2, neurodegeneration 3 2349 2.62
PPIA Peptidylprolyl Isomerase A Protein Coding 57 Parkinson’s Disease, LRRK2, neurodegeneration 3 2366 2.55
UBE2K Ubiquitin Conjugating Enzyme E2 K Protein Coding 51 Parkinson’s Disease, LRRK2, neurodegeneration 3 2388 2.49
COPS5 COP9 Signalosome Subunit 5 Protein Coding 51 Parkinson’s Disease, LRRK2, neurodegeneration 3 2450 2.31
PDHA1 Pyruvate Dehydrogenase E1 Alpha 1 Subunit Protein Coding 59 Parkinson’s Disease, LRRK2, neurodegeneration 3 2547 2.04
DDX1 DEAD-Box Helicase 1 Protein Coding 51 Parkinson’s Disease, neurodegeneration 2 2528 1.71
ANXA7 Annexin A7 Protein Coding 51 late-onset, neurodegeneration 2 2571 1.60
YARS Tyrosyl-TRNA Synthetase Protein Coding 53 late-onset, neurodegeneration 2 2576 1.60
PSMD12 Proteasome 26S Subunit, Non-ATPase 12 Protein Coding 49 Parkinson’s Disease, LRRK2, neurodegeneration 3 2710 1.50
EPS15 Epidermal Growth Factor Receptor Pathway Substrate 15 Protein Coding 54 Parkinson’s Disease, LRRK2 2 2701 1.26
PIK3CB Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Beta Protein Coding 57 LRRK2, neurodegeneration 2 2746 1.11
MDH1 Malate Dehydrogenase 1 Protein Coding 55 Parkinson’s Disease, neurodegeneration 2 2770 1.04
ATP6V1B2 ATPase H+ Transporting V1 Subunit B2 Protein Coding 56 LRRK2, neurodegeneration 2 2775 1.03
GABARAPL2 GABA Type A Receptor Associated Protein Like 2 Protein Coding 55 Parkinson’s Disease 1 2652 0.99
IARS2 Isoleucyl-TRNA Synthetase 2, Mitochondrial Protein Coding 49 Parkinson’s Disease 1 2681 0.94
STRAP Serine/Threonine Kinase Receptor Associated Protein Protein Coding 45 LRRK2, neurodegeneration 2 2823 0.88
FOSL1 FOS Like 1, AP-1 Transcription Factor Subunit Protein Coding 52 LRRK2, neurodegeneration 2 2826 0.87
ICK Intestinal Cell Kinase Protein Coding 53 Parkinson’s Disease 1 2711 0.87
TXNL1 Thioredoxin Like 1 Protein Coding 47 late-onset 1 2741 0.79
TMEM30A Transmembrane Protein 30A Protein Coding 46 Parkinson’s Disease, LRRK2 2 2895 0.62
RRAS RAS Related Protein Coding 52 LRRK2 1 2853 0.54
PRDM4 PR/SET Domain 4 Protein Coding 43 LRRK2 1 2853 0.54
NPTN Neuroplastin Protein Coding 49 neurodegeneration 1 2878 0.49
ATP6V1H ATPase H+ Transporting V1 Subunit H Protein Coding 48 LRRK2 1 2905 0.39
NME1 NME/NM23 Nucleoside Diphosphate Kinase 1 Protein Coding 57 neurodegeneration 1 2920 0.34
REEP5 Receptor Accessory Protein 5 Protein Coding 46 LRRK2 1 2936 0.28
SUCLA2 Succinate-CoA Ligase ADP-Forming Beta Subunit Protein Coding 57 LRRK2 1 2936 0.28
BCAS2 BCAS2, Pre-MRNA Processing Factor Protein Coding 46 LRRK2 1 2938 0.27
SF3A2 Splicing Factor 3a Subunit 2 Protein Coding 46 LRRK2 1 2938 0.27
HLTF Helicase Like Transcription Factor Protein Coding 48 LRRK2 1 2938 0.27
RAB22A RAB22A, Member RAS Oncogene Family Protein Coding 44 LRRK2 1 2938 0.27
RAN RAN, Member RAS Oncogene Family Protein Coding 54 neurodegeneration 1 2958 0.10
PTBP2 Polypyrimidine Tract Binding Protein 2 Protein Coding 47 neurodegeneration 1 2959 0.07

Indirect VarElect Results

Implicated Symbol Implicating Symbol Description Category GIFTs Matched Phenotypes Matched Phenotypes Count Global Rank (Total Genes 11967) Score (Implicated)
UBE2V2 PRKN Parkin RBR E3 Ubiquitin Protein Ligase Protein Coding 47 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 3 23.14
UBE2V2 RPS27A Ribosomal Protein S27a Protein Coding 53 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 45 23.14
UBE2V2 FBXO7 F-Box Protein 7 Protein Coding 50 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 16 23.14
UBE2V2 UCHL1 Ubiquitin C-Terminal Hydrolase L1 Protein Coding 62 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 7 23.14
UBE2V2 UBE2E2 Ubiquitin Conjugating Enzyme E2 E2 Protein Coding 49 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 145 23.14
SNAP91 SNCA Synuclein Alpha Protein Coding 61 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 2 13.14
SNAP91 PRKN Parkin RBR E3 Ubiquitin Protein Ligase Protein Coding 47 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 3 13.14
SNAP91 SYNJ1 Synaptojanin 1 Protein Coding 57 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 33 13.14
SNAP91 DNAJC6 DnaJ Heat Shock Protein Family (Hsp40) Member C6 Protein Coding 51 Parkinson’s Disease, LRRK2, late-onset 3 27 13.14
SNAP91 UCHL1 Ubiquitin C-Terminal Hydrolase L1 Protein Coding 62 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 7 13.14
TERF2IP UCHL1 Ubiquitin C-Terminal Hydrolase L1 Protein Coding 62 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 7 12.55
TERF2IP SNCA Synuclein Alpha Protein Coding 61 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 2 12.55
TERF2IP AKT1 AKT Serine/Threonine Kinase 1 Protein Coding 65 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 79 12.55
TERF2IP RPS27A Ribosomal Protein S27a Protein Coding 53 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 45 12.55
TERF2IP TBP TATA-Box Binding Protein Protein Coding 57 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 40 12.55
PYCARD BAX BCL2 Associated X, Apoptosis Regulator Protein Coding 57 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 107 9.78
PYCARD NLRP3 NLR Family Pyrin Domain Containing 3 Protein Coding 56 Parkinson’s Disease, late-onset 2 222 9.78
PYCARD PRKN Parkin RBR E3 Ubiquitin Protein Ligase Protein Coding 47 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 3 9.78
PYCARD CASP3 Caspase 3 Protein Coding 61 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 56 9.78
PYCARD SQSTM1 Sequestosome 1 Protein Coding 59 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 48 9.78
SRPRB SNCA Synuclein Alpha Protein Coding 61 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 2 8.42
SRPRB PRKN Parkin RBR E3 Ubiquitin Protein Ligase Protein Coding 47 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 3 8.42
SRPRB RPS27A Ribosomal Protein S27a Protein Coding 53 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 45 8.42
SRPRB UCHL1 Ubiquitin C-Terminal Hydrolase L1 Protein Coding 62 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 7 8.42
SRPRB SNCAIP Synuclein Alpha Interacting Protein Protein Coding 52 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 8 8.42
EIF1B EIF4G1 Eukaryotic Translation Initiation Factor 4 Gamma 1 Protein Coding 55 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 36 7.94
EIF1B UCHL1 Ubiquitin C-Terminal Hydrolase L1 Protein Coding 62 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 7 7.94
EIF1B RPS27A Ribosomal Protein S27a Protein Coding 53 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 45 7.94
EIF1B SOD2 Superoxide Dismutase 2 Protein Coding 60 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 78 7.94
EIF1B GAPDH Glyceraldehyde-3-Phosphate Dehydrogenase Protein Coding 58 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 98 7.94
MRPL15 PARK7 Parkinsonism Associated Deglycase Protein Coding 56 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 5 7.78
MRPL15 RPS27A Ribosomal Protein S27a Protein Coding 53 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 45 7.78
MRPL15 NDUFS4 NADH:Ubiquinone Oxidoreductase Subunit S4 Protein Coding 52 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 31 7.78
MRPL15 TH Tyrosine Hydroxylase Protein Coding 62 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 24 7.78
MRPL15 EIF4G1 Eukaryotic Translation Initiation Factor 4 Gamma 1 Protein Coding 55 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 36 7.78
LYL1 GDNF Glial Cell Derived Neurotrophic Factor Protein Coding 59 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 52 7.74
LYL1 PLAU Plasminogen Activator, Urokinase Protein Coding 63 LRRK2, late-onset 2 162 7.74
LYL1 NFKB1 Nuclear Factor Kappa B Subunit 1 Protein Coding 63 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 409 7.74
LYL1 ZEB1 Zinc Finger E-Box Binding Homeobox 1 Protein Coding 57 late-onset 1 273 7.74
LYL1 BAX BCL2 Associated X, Apoptosis Regulator Protein Coding 57 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 107 7.74
XRCC2 RPS27A Ribosomal Protein S27a Protein Coding 53 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 45 6.43
XRCC2 NBN Nibrin Protein Coding 55 Parkinson’s Disease, late-onset, neurodegeneration 3 388 6.43
XRCC2 TP53 Tumor Protein P53 Protein Coding 65 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 201 6.43
XRCC2 COMT Catechol-O-Methyltransferase Protein Coding 61 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 34 6.43
XRCC2 ATM ATM Serine/Threonine Kinase Protein Coding 64 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 498 6.43
BMP8B PLA2G6 Phospholipase A2 Group VI Protein Coding 57 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 12 6.27
BMP8B BDNF Brain Derived Neurotrophic Factor Protein Coding 59 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 42 6.27
BMP8B MAPK14 Mitogen-Activated Protein Kinase 14 Protein Coding 62 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 89 6.27
BMP8B IL10 Interleukin 10 Protein Coding 57 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 243 6.27
BMP8B GDNF Glial Cell Derived Neurotrophic Factor Protein Coding 59 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 52 6.27
LAPTM4B GBA Glucosylceramidase Beta Protein Coding 59 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 11 5.59
LAPTM4B ABCB1 ATP Binding Cassette Subfamily B Member 1 Protein Coding 61 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 449 5.59
LAPTM4B NEDD4 Neural Precursor Cell Expressed, Developmentally Down-Regulated 4, E3 Ubiquitin Protein Ligase Protein Coding 55 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 669 5.59
LAPTM4B SLC11A2 Solute Carrier Family 11 Member 2 Protein Coding 58 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 132 5.59
LAPTM4B NFE2L2 Nuclear Factor, Erythroid 2 Like 2 Protein Coding 56 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 351 5.59
ADSS GBA Glucosylceramidase Beta Protein Coding 59 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 11 4.39
ADSS PLA2G6 Phospholipase A2 Group VI Protein Coding 57 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 12 4.39
ADSS GAD1 Glutamate Decarboxylase 1 Protein Coding 61 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 120 4.39
ADSS APOE Apolipoprotein E Protein Coding 61 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 13 4.39
ADSS MAPK14 Mitogen-Activated Protein Kinase 14 Protein Coding 62 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 89 4.39
BTBD3 CUL1 Cullin 1 Protein Coding 55 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 143 1.47
BTBD3 SKP1 S-Phase Kinase Associated Protein 1 Protein Coding 52 Parkinson’s Disease, LRRK2, neurodegeneration 3 310 1.47
BTBD3 E2F1 E2F Transcription Factor 1 Protein Coding 53 Parkinson’s Disease, LRRK2, neurodegeneration 3 1777 1.47
BTBD3 DAPK1 Death Associated Protein Kinase 1 Protein Coding 57 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 823 1.47
BTBD3 PLCB1 Phospholipase C Beta 1 Protein Coding 57 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 1019 1.47
RTCA LMNB1 Lamin B1 Protein Coding 57 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 228 1.23
RTCA NOP56 NOP56 Ribonucleoprotein Protein Coding 51 Parkinson’s Disease, late-onset, neurodegeneration 3 373 1.23
RTCA IL6 Interleukin 6 Protein Coding 59 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 197 1.23
RTCA HNRNPA1 Heterogeneous Nuclear Ribonucleoprotein A1 Protein Coding 56 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 538 1.23
RTCA TNF Tumor Necrosis Factor Protein Coding 63 Parkinson’s Disease, LRRK2, late-onset, neurodegeneration 4 185 1.23

EnrichR Enrichment

KEGG

KEGG

Wikipathways

Wikipathways

Reactome

Reactome

GO Cellular Component

GO Cellular Component

GO Biological Process

GO Biological Process

GO Molecular Function

GO Molecular Function